RESUMO
BACKGROUND: Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). RESULTS: The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33-3.38). CONCLUSIONS: P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis.
Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias Penianas , Masculino , Humanos , Neoplasias Penianas/genética , Neoplasias Penianas/epidemiologia , Neoplasias Penianas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/epidemiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Prognóstico , 5-Metilcitosina , Metilação de DNA , Recidiva Local de Neoplasia/genética , Papillomaviridae/genética , Carcinoma de Células Escamosas/metabolismo , Alphapapillomavirus/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Epigênese Genética , DNA ViralRESUMO
ABSTRACT: Studies have been performed to identify the proteins present in canine seminal plasma (SP) and relate them to sperm quality as well as to discover molecular markers of reproductive tract diseases. There is evidence that heparin-binding proteins, zinc-binding proteins, and lactoferrin as well as the matrix metalloproteinase, superoxide dismutase, catalase, and glutathione peroxidase enzymes are associated with canine sperm quality. Other studies indicate that prolactin and enzymes like arginine esterase, acid phosphatase, and alkaline phosphatase could be successfully used as biomarkers of reproductive disorders. Thus, the present literature review aims to address aspects related to proteins of the canine SP, their influence on fertility, and their importance as biomarkers of reproductive disorders.
RESUMO: Pesquisas têm sido realizadas para identificar as proteínas presentes no plasma seminal canino, com o intuito de relacioná-las com a qualidade espermática, bem como buscar por marcadores moleculares de patologias do trato reprodutivo. Há evidências de que as proteínas ligadoras de heparina, ligadoras de zinco, a lactoferrina, bem como as enzimas matrix metalloproteinase, superoxide dismutase, catalase e a glutationa peroxidase estão relacionadas com a qualidade seminal canina. Outras pesquisas indicam que a prolactina, e as enzimas arginina esterase, fosfatase ácida e fosfatase alcalina poderiam ser utilizadas com sucesso como biomarcadores de doenças reprodutivas. Assim, esta revisão de literatura objetiva abordar aspectos relacionados às proteínas do plasma seminal canino, suas influências sobre a fertilidade, e sua importância como biomarcadores de doenças reprodutivas.
RESUMO
The role of activin-A in follicular development and on the mRNA expression levels of different genes in goat secondary follicles was evaluated. Goat secondary follicles (≥ 150 µm) were cultured for 18 days under control conditions or with the addition of either 50 or 100 ng/ml activin-A (Experiment 1). The mRNA levels for the genes that code for activin-A, ActR-IA, ActR-IB, ActR-IIA, ActR-IIB, follicle stimulating hormone receptor (FSH-R) and P450 aromatase were measured in each condition (Experiment 2). We observed that after 6 days of culture, the antrum formation rate was higher in cultures with added activin-A than in the cultured control (P < 0.05). The addition of 50 ng/ml activin-A increased the follicular growth rate in the final third of the culture (days 12-18), resulting in a higher percentage of meiosis resumption (P < 0.05). On day 6, the addition of activin-A (50 ng/ml) increased the levels of ActR-IA mRNA compared with the cultured control (P < 0.05). After 18 days, the addition of 50 ng/ml activin-A significantly increased the levels of its own mRNA compared with the non-cultured control. Moreover, this treatment reduced the mRNA levels of P450 aromatase in comparison with the cultured control (P < 0.05). Higher levels of P450 aromatase mRNA were found for both activin-A treatments compared with the non-cultured control (P < 0.05). No difference in estradiol levels was detected among any of the tested treatments. In conclusion, the addition of activin-A to culture medium stimulated early antrum formation as well as an increase in the daily follicular growth rate and the percentage of meiosis resumption.